AJP - Endocrinology and Metabolism, Vol 250, Issue 5 512-E517, Copyright © 1986 by American Physiological Society
TRH and GRF stimulate release of growth hormone through different mechanisms
M. Szabo
Thyrotropin-releasing hormone (TRH) is an effective stimulator of growth
hormone (GH) release from cultured adenohypophysial cells of chronically
hypothyroid rats in vitro. The present study explored the question of cAMP
and calcium mediation of the GH-stimulatory effect of TRH in this system. A
maximally stimulatory concentration of TRH was added together with various
concentrations of human GH-releasing factor 40 (hGRF-40) whose action is
cAMP mediated, or of dibutyryl cAMP (DBcAMP), to primary monolayer cultures
of adenohypophysial cells from thyroidectomized rats. The GH responses to
the combined addition of TRH with all doses of GRF or DBcAMP were fully
additive, causing parallel elevations of the dose-response curves. Whereas
the GH response to maximally effective concentrations of hGRF-40 and
DBcAMP, added together, was not greater than that to either secretagogue
alone, the inclusion of TRH increased the response to a new Emax. The
calcium inhibitors, verapamil, EGTA, and CoCl2, markedly suppressed basal
GH release and virtually completely blocked the GH response to TRH,
suggesting calcium mediation. In chronically hypothyroid,
urethan-anesthetized rats, the in vivo effect of the combined
administration of maximally effective doses of TRH and GRF on plasma GH
levels was also additive. These findings indicate that TRH stimulates GH
release in adenohypophysial cells of hypothyroid rats by a
cAMP-independent, calcium-dependent mechanism.
